The objectives of the proposed research are to isolate, purify, and determine the precise molecular structure of vasodepressor lipids excluding prostaglandins, from human tissues. Emphasis will be placed on lipids which inhibit human renin and/or angiotensin I converting enzyme activity. The project is comprised of four major objectives; (1) to determine the precise structure of human renin and/or converting enzyme lipid inhibitors; (2) to determine the histological area of the human kidney which contains the lipid inhibitors, i.e., cortex or medullar portions; (3) to determine the biosynthesis of the lipid inhibitors; and (4) to determine the existence and structure of lipid inhibitors in human plasma and erythrocytes. Neutral and phospholipids will be purified into homogenous lipid classes and assayed for vasodepressor activity as well as renin and angiotensin I converting enzyme inhibition. The active lipids will then be chemically characterized by a variety of techniques which include (1) special TLC techniques such as reverse-phase and argentation chromatography; (2) gas chromatography; (3) enzymatic and chemical degradation schemes; (4) auto-amino acid analysis; and (5) IR and mass spectrometry. The same methodological approach will be used to determine the presence of inhibitory lipids in the medulla and cortex portion of the human kidney as well as their existence in human plasma and erythrocytes. Biosynthesis experiments will be performed on the vasoactive lipids by utilizing appropriate radioactive precursors in conjunction with incubation and isolation techniques. BIBLIOGRAPHIC REFERENCES: Overturf, M., R.E. Druilhet and W.M. Kirkendall. 1976. Effects of human lipids on human kidney renin activity. Biochemical Pharmacol. 25:2443-2453. Kirkendall, W.M. and M. Overturf. 1976. Renal artery hypertension: Diagnosis and treatment. Urology Digest.